Summary Existing studies suggest that tissue elasticity is possibly correlated with the aggressiveness of cancers. Based on results from deformable image registration, the proposed project investigates the possibility of tracking the organs movement subject to external forces and geometric constraints, thereby deducing patient- specific tissue elasticity parameters for proactive health monitoring. The objectives of this exploratory research project are (1) to develop a computational framework based on extensive studies of a large cohort of cancer patients, in order to accurately estimate patent-specific tissue elasticity using a coupled biomechanical simulation-optimization framework on a pair of medical images (possibly from ultrasound, mammography, computed tomography scan, magnetic resonance imaging, or other imaging technologies); (2) to examine potential associations between tissue elasticity in different regions with aggressiveness of known/diagnosed cancer in the corresponding regions; (3) to derive predictive models for cancer staging/grading based on recovered patient-specific tissue elasticity and other explanatory variables; (4) to design a health monitoring system based on individualized analysis of tissue elasticity for 'at-risk' groups who are more likely to develop cancers. This proposal describes a truly ambitious effort and a bold vision that is built upon the investigators' prior scientific accomplishments and strong credentials to potentially transform existing practice to more proactive, preventive, evidence-based health monitoring for individuals at risk of developing cancers. This research is expected to make several major scientific advances. These include new algorithms for non-invasive, image based techniques for automatic extraction of tissue elasticity parameters without force applications and/or force sensing devices, novel regression models and inference procedures for survival analysis, new predictive models for cancer staging and grading based on patient-specific tissue elasticity parameters, and a health monitoring system for at-risk groups based on individual tissue elasticity along with other variables.